Measuring the systemic effects of inhaled beclomethasone: timed morning urine collections compared with 24 hour specimens

Abstract

Background: Inhaled glucocorticoid therapy has systemic effects including hypothalamic-pituitary-adrenal (HPA) suppression. The optimal test for detecting these effects has not been defined.

Methods: Timed urine collections and 09.00 hour plasma cortisol levels were obtained from 12 normal volunteers receiving inhaled placebo, beclomethasone (BDP) 800 or 2000 micrograms/day. The 24 hour urine samples were collected as follows: first hour after waking (hour 1), the next two hours after waking (hours 2 and 3), remainder of day, and overnight, with results expressed as urine cortisol/creatinine (UCC) ratios and as hourly cortisol output in the timed collections. Twenty four hour urinary cortisol excretion was also calculated. Medication was blinded and given in random order with a washout period of at least 11 days between each treatment arm.

Results: None of the UCC ratios changed with BDP 800 micrograms/day. UCC ratios at hour 1, hour 2 and 3, and overnight, and 24 hour urinary free cortisol excretion were reduced after BDP 2000 micrograms/day, whilst remainder of day UCC ratio and the plasma cortisol level did not change significantly. Cortisol output showed similar changes. In a follow up study BDP 1400 micrograms/day also reduced UCC ratios for the first two hours after waking.

Conclusions: UCC ratios are as sensitive as the more cumbersome 24 hour urinary free cortisol excretion, and more sensitive than single morning plasma cortisol measurements, in detecting the effects of inhaled beclomethasone on the HPA axis.